Linaclotide for treatment of constipation - minimally absorbed peptide agonist of guanylate cyclase C receptor

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. It consists of 14 amino acids. The sequence is:

H–Cys1–Cys2–Glu3–Tyr4–Cys5–Cys6–Asn7–Pro8–Ala9–Cys10–Thr11–Gly12–Cys13–Tyr14–OH

Two randomized, 12-week trials included 1,300 patients with chronic constipation (NEJM, 2011). Patients received either placebo or linaclotide once daily for 12 weeks.

The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in linaclotide groups.

Linaclotide reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks of linaclotide in chronic constipation.

References:

Two Randomized Trials of Linaclotide for Chronic Constipation. N Engl J Med 2011; 365:527-536August 11, 2011.

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